UNDESTANDING THE RSPO2 ROLE IN SWINE OOCYTE MATURATION AND EMBRYONIC DEVELOPMENT

• Grant number: 25/03340-4
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Agronomical Sciences - Veterinary Medicine - Animal Reproduction
• Principal Investigator: Flávio Vieira Meirelles
• Grantee: Thais Naomi Goncalves Nesiyama
• Supervisor: Vilceu Bordignon
• Host Institution: Faculdade de Zootecnia e Engenharia de Alimentos (FZEA). Universidade de São Paulo (USP). Pirassununga , SP, Brazil
• Institution abroad: McGill University, MacDonald, Canada
• Associated to the scholarship: 23/12977-0 - Manipulation of the Wnt/b-catenin pathway during pig´s oocytes IVM aiming to produce clones by SCNT, BP.DD

Abstract

Biomedical models are essential to understanding human diseases and developing treatments. Rodents are generally favored due to their small size and low costs, but recently, swine species have increased interest due to their physiological and genetic similarities to humans. Genetically edited swine, utilizing CRISPR/Cas9 and somatic cell nuclear transfer (SCNT), have been established as valuable models. However, challenges remain, such as low zygote reconstruction rates (0-15%) requiring an extensive number of oocytes. In vitro maturation (IVM) presents obstacles, particularly regarding oocyte competence. In addition, these oocytes are also helpful for studying developmental mechanisms. Recent studies highlight the importance of communication between oocytes and granulosa cells mediated by transzonal projections and various signaling pathways, including the WNT/¿-catenin pathway. The R-spondin 2 (RSPO2) protein is crucial for granulosa cell proliferation, interacting with the WNT pathway, thus influencing oocyte development and fertility. During IVM, modulating RSPO2 and Dickkopf-related protein 1 (DKK1) can enhance oocyte maturation rates and embryo development. Based on the research findings of our current project (2023/12977-0), these modulations indicate improvements in blastocyst rates when RSPO2 is added to the IVM medium. Therefore, more studies are necessary to understand the mechanisms of the WNT/¿-catenin pathways and the importance of the RSPO2. For this, we aim in this international internship to interfere in WNT pathways such as RSPO2 and the receptor LGR6, in oocytes and granulosa cells to explore its role in ¿-catenin activation and assess the implications for oocyte maturation, granulosa cell proliferation, embryo development post-SCNT, with the expect to understand better the swine reproductive mechanisms.